P400: COMPARISON OF MORPHOLOGICAL &amp; MRD RESPONSE WITH DEXAMETHASONE VERSUS PREDNISOLONE IN BFM 2009 INDUCTION THERAPY IN PEDIATRIC AND AYA ACUTE LYMPHOBLASTIC LEUKEMIA: A SINGLE-CENTER STUDY FROM INDIA
Authors: Karthik Kumar, Sashi Kant Singh, Jhasaketan Nayak, Kanimozhi M, Adamya Gupta, Paras Satadeve, Aishwarya Muralidharan, Pratibha Singh, Kavya Ronanki, Vinod Kumar, Priyavadhana B, Gaurav Dhingra, Puneet Dhamija, Harish Chandra, Uttam Kumar Nath
Journal: HemaSphere (2023)

Background: Acute lymphoblastic leukemia (ALL) is the commonest cancer in children. With the evolution of MRD adapted intensive treatment regimens in children & AYA with ALL, survival rates have improved significantly. Multiple studies showed dexamethasone (Dexa) had superior response than prednisone (Pred) in high-risk ALL & had decreased cumulative relapse, but at the cost of increased toxicity. Our randomized controlled study compared efficacy & safety of Dexa & Pred in ALL BFM 2009 induction phase therapy in pediatric & adolescent ALL, as there is no published data from India. Aims: • To compare post-induction (day 33) complete remission (CR) & Flowcytometric MRD rates in the two treatment groups. • To compare day 8 steroid response, and day 15 bone marrow (BM) morphological & MRD response in the two groups. • To compare the adverse events in the two groups. Methods: Our study enrolled treatment-naïve ALL patients of 1-25 years’ age from April 2021 to February 2023. Patients were randomized to receive either Dexa 10 mg/m2/day i.v. for 1-14 days or Pred 60 mg/m2/day p.o. for 28 days during Induction Phase IA of ALL BFM 2009 regimen. Steroid dose was tapered over next 7 days in both groups. Infantile ALL & lymphoblastic lymphoma were excluded. The adverse events were compared as per NCI-CTCAE v-5. Results: Total 74 patients were enrolled [Dexa 39 (53%); Pred 35 (47%)]. Median age was 8 years, with M: F ratio 1.6: 1. B-cell ALL accounted for 80% of total. The distribution of patients in standard-risk, intermediate-risk, & high-risk groups were 8%, 53%, & 39% respectively. At diagnosis, 28% patients had hyperleukocytosis, 15% had bacterial sepsis, 4% had invasive fungal infection, and 8% had CNS leukemia. Dexa group had higher proportion of Ph positive patients (12% vs 2%, p=0.07). Of total 74 patients, 76% have completed induction therapy, & 7% patients are currently on induction. Eight patients died before completion, & 5 patients discontinued induction. Overall, 81% patients had good steroid response (blood blast count <1000/µl) on day 8. On day 15, 74% of patients had M1 marrow. Overall, 38% patients had day 15 BM MRD <0.1%. Morphological CR was documented in 89% of available patients on day 33 [Dexa 100%; Pred 76%; p=0.003]. On day 33, overall 77% patients achieved negative MRD status (BM Flow-MRD <0.01 %). Thus, day 33 CR rate was significantly higher in Dexa group. However, the differences in day 8 steroid response, day 15 morphological & MRD responses, & day 33 MRD response in the two steroid groups were not statistically significant. The common hematological AE observed in the study were thrombocytopenia, neutropenia, lymphopenia, anemia, febrile neutropenia, & invasive fungal infections. Dexa group had higher incidence of neutropenia & lymphopenia [p:0.05]. The common non-hematological AE were proximal myopathy, typhlitis, & hypofibrinogenemia. There was no incidence of osteonecrosis & psychosis in the study. The rest of the AEs were not significant. There were 8 deaths (10%) in induction [Dexa = 5, Pred = 3] [p: 0.5]; causes of death were MDR bacterial infections [n=4], invasive fungal infections [n=2], intracranial hemorrhage [n=1], & COVID-19 infection [n=1]. Summary/Conclusion: In our single-centre experience, use of dexamethasone in induction phase of ALL BFM 2009 regimen in pediatric & adolescent ALL was associated with achievement of significantly higher post-induction complete remission rate compared to prednisolone, without significant differences in day 15 & day 33 Flow-MRD responses, & overall treatment-related adverse events in the two steroid groups.Keywords: Minimal residual disease (MRD), Acute lymphoblastic leukemia